Unweighted regression models perform better than weighted regression techniques for respondent-driven sampling data: results from a simulation study

Background: It is unclear whether weighted or unweighted regression is preferred in the analysis of data derived from respondent driven sampling. Our objective was to evaluate the validity of various regression models, with and without weights and with various controls for clustering in the estimation of the risk of group membership from data collected using respondent-driven sampling (RDS). Methods: Twelve networked populations, with varying levels of homophily and prevalence, based on a known distribution of a continuous predictor were simulated using 1000 RDS samples from each population. Weighted and unweighted binomial and Poisson general linear models, with and without various clustering controls and standard error adjustments were modelled for each sample and evaluated with respect to validity, bias and coverage rate. Population prevalence was also estimated. Results: In the regression analysis, the unweighted log-link (Poisson) models maintained the nominal type-I error rate across all populations. Bias was substantial and type-I error rates unacceptably high for weighted binomial regression. Coverage rates for the estimation of prevalence were highest using RDS-weighted logistic regression, except at low prevalence (10%) where unweighted models are recommended. Conclusions: Caution is warranted when undertaking regression analysis of RDS data. Even when reported degree is accurate, low reported degree can unduly influence regression estimates. Unweighted Poisson regression is therefore recommended.York University Librarie

Concert recording 2013-11-19

[Track 01]. Western fanfare / Eric Ewazen -- [Track 02]. Little sketches / Ivan Elozovic -- [Track 03]. Preludium / Krysztof Penderecki -- [Track 04]. Abime des oiseaux from Quatour pour la fin du temps / Olivier Messiaen -- [Track 05]. Scherzino / Walter Hartley -- [Track 06]. Quintet for winds, no. 2. II ; [Track 07]. III / David Maslanka -- [Track 08]. String quartet, no. 3. III / Dmitri Shostakovich

Health-related quality of life results from the phase III CheckMate 067 study

Background Nivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which could result in diminished health-related quality of life (HRQoL). Here we report analyses of HRQoL for patients with advanced melanoma in clinical trial CheckMate 067.Patients and methods HRQoL was assessed at weeks 1 and 5 per 6-week cycle for the first 6 months, once every 6 weeks thereafter, and at two follow-up visits using the European Organization for Research and Treatment of Care Core Quality of Life Questionnaire and the EuroQoL Five Dimensions Questionnaire. In addition to the randomised population, patient subgroups, including BRAF mutation status, partial or complete response, treatment-related AEs of grade 3/4, and those who discontinued due to any reason and due to an AE, were investigated.Results Nivolumab and ipilimumab combination and nivolumab alone both maintained HRQoL, and no clinically meaningful deterioration was observed over time compared with ipilimumab. In addition, similar results were observed across patient subgroups, and no clinically meaningful changes in HRQoL were observed during follow-up visits for patients who discontinued due to any cause.Conclusion These results further support the clinical benefit of nivolumab monotherapy and nivolumab and ipilimumab combination therapy in patients with advanced melanoma. The finding that the difference in grade 3/4 AEs between the arms did not translate into clinically meaningful differences in the reported HRQoL may be relevant in the clinical setting.Study number NCT01844505

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

945 patients with inoperable stage III or stage IV melanoma were randomised to ipilimumab plus nivolumab (ipi/nivo)(314), nivolumab (nivo) (316) or ipilimumab (Ipilimumab) (315). The minimum follow up from randomisation of the last patient was 60 months. Objective responses were seen in 58% of Ipilimumab/nivo, 45% of nivo and 19% of Ipilimumab patients. Complete responses were seen in 22% (Ipilimumab/nivo), 19% (nivo) and 6% (Ipi) patients. Overall survival (OS) at five years was 52% (Ipilimumab/nivo), 44% (nivo) and 26% (Ipi). In patients with and without bras mutations the OS at five years was 60 & 48% (Ipilimumab/nivo), 46 & 43% (nivo) and 30 & 25% (Ipi) respectively. OS curves were flat beyond three years indicating that these treatments lead to sustained long term survival of these patients

Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma

PURPOSE In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. PATIENTS AND METHODS Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated. RESULTS Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF–wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed. CONCLUSION These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy

Disparities in Healthcare Utilisation Rates for Aboriginal and Non-Aboriginal Albertan Residents, 1997-2006: A Population Database Study

Background: It is widely recognised that significant discrepancies exist between the health of indigenous and nonindigenous populations. Whilst the reasons are incompletely defined, one potential cause is that indigenous communities do not access healthcare to the same extent. We investigated healthcare utilisation rates in the Canadian Aboriginal population to elucidate the contribution of this fundamental social determinant for health to such disparities. Methods: Healthcare utilisation data over a nine-year period were analysed for a cohort of nearly two million individuals to determine the rates at which Aboriginal and non-Aboriginal populations utilised two specialties (Cardiology and Ophthalmology) in Alberta, Canada. Unadjusted and adjusted healthcare utilisation rates obtained by mixed linear and Poisson regressions, respectively, were compared amongst three population groups - federally registered Aboriginals, individuals receiving welfare, and other Albertans. Results: Healthcare utilisation rates for Aboriginals were substantially lower than those of non-Aboriginals and welfare recipients at each time point and subspecialty studied [e.g. During 2005/06, unadjusted Cardiology utilisation rates were 0.28% (Aboriginal, n = 97,080), 0.93% (non-Aboriginal, n = 1,720,041) and 1.37% (Welfare, n = 52,514), p = ,0.001]. The age distribution of the Aboriginal population was markedly different [2.7%$65 years of age, non-Aboriginal 10.7%], and comparable utilisation rates were obtained after adjustment for fiscal year and estimated life expectancy [Cardiology: Incidence Rate Ratio 0.66, Ophthalmology: IRR 0.85]. Discussion: The analysis revealed that Aboriginal people utilised subspecialty healthcare at a consistently lower rate than either comparatively economically disadvantaged groups or the general population. Notably, the differences were relatively invariant between the major provincial centres and over a nine year period. Addressing the causes of these discrepancies is essential for reducing marked health disparities, and so improving the health of Aboriginal people

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

This is the three year update of a randomised phase III trial in patients with locally advanced inoperable stage III or stage IV melanoma. 1296 patients were radomised to receive either ipilimumab (Ipi), nivolumab (Nivo) or both antibodies (Ipi+Nivo). Complete responses were seen in 5, 16 & 19% of patients in the Ipi, Nivo and Ipi+Nivo groups respectively. Partial responses were seen in 14, 28 & 29% of patients respectively. With a minimum follow up of 28 months 3 year overall survivals were 32, 52 & 58% in the Ipi, Nivo & Ipi+Nivo respectively. In patients with braf mutations the three year survivals were 37, 56 & 68% in the three groups. This compares with a three year survival of 44% in the dabrafenib plus trametinib arm of the COMBI-D trial (J. Clin. Oncol. 2017 Dob: 10.1200/JCO.2017.74.1025). These data represent practice changing data for oncologist who treat melanoma and life changing treatment for patients with metastatic melanoma